6-Bromomethyl-4H-1,3-dioxin: a versatile bromomethyl vinyl ketone equivalent for heterocycle and carbocycle construction.

6-Bromomethyl-4H-1,3-dioxin has been prepared in three steps from allyl iodide. A variety of enolates were then alkylated with this bromide. The resulting 6-alkyl-4H-1,3-dioxins were either subjected to further multistep transformations and/or heated to effect facile retrocycloaddition reactions. The resulting enones smoothly participated in novel endo-conjugate addition reactions with both carbon and nitrogen nucleophiles. For example, several bicyclo[4.3.1]decan-3,10-diones, the carbon framework of the CP compounds, were constructed using this novel annulation strategy. In another natural product study, a benzazocine related to the heterocyclic framework of the ring-opened tautomeric form of FR-900482 was also prepared using this methodology. Finally, a piperidin-4-one obtained from a 6-endo conjugate addition was converted to the naturally occurring (2S,4R)-4-hydroxypipecolic acid. Collectively, these examples document the synthetic equivalency of dioxin 1 with bromomethyl vinyl ketone and, moreover, delineate a strategy for accomplishing the sequential reactions with nucleophiles at the alpha' followed by the beta electrophilic sites.